CALGB 9741: What the Breast Cancer Trial Found

A trial about timing, not drugs

CALGB 9741 did not test a new medicine. It tested a calendar.

Everyone in the trial received the same three chemotherapy drugs at the same doses: doxorubicin, paclitaxel, and cyclophosphamide. The question was whether giving them every 2 weeks instead of every 3 weeks would work better.

That idea has a name. Dose-dense chemotherapy means shortening the gap between cycles rather than raising the dose. The reasoning is that tumor cells regrow between treatments, so a shorter gap gives them less time to recover.

Who took part

2,005 women with node-positive primary breast cancer, meaning the cancer had reached lymph nodes in the armpit. All had already had surgery. This was adjuvant treatment: chemotherapy given after surgery to lower the chance of the cancer returning.

The design tested two things at once, in a 2x2 arrangement. Women were randomly assigned to every-2-week or every-3-week dosing, and separately to receiving the drugs one after another or with two given together. Results were published in the Journal of Clinical Oncology in 2003.

Every-2-week dosing required filgrastim, an injected growth factor that prompts the bone marrow to produce white blood cells faster.

What the trial found

Dose-dense treatment improved the main measure, disease-free survival — time without the cancer returning.

• Risk ratio 0.74, P=0.010. That is roughly a 26% lower risk of relapse or death.
• In plain numbers, 82% of women on the every-2-week schedule were alive and cancer-free at 4 years, against 75% on the every-3-week schedule.
• Overall survival also improved: risk ratio 0.69, P=0.013.

The sequence question came out flat. Giving the drugs one at a time worked as well as giving two together, with no interaction between the two variables.

The safety result surprised people. Severe neutropenia — a dangerously low count of the white cells that fight bacteria — was less frequent on the compressed schedule, because of the growth factor support.

Why it changed practice

The trial showed that when to give chemotherapy is a lever in its own right, separate from what to give or how much.

Every-2-week schedules became a standard option for adjuvant chemotherapy in node-positive breast cancer, and the dose-dense principle has been applied elsewhere since. The compressed course also finishes sooner, which matters to people living through it.

Where breast cancer stands now

ACS estimates 321,910 new cases of female breast cancer in the United States for 2026, a projection SEER reprints; NCI's own SEER data put 5-year relative survival at 91.9% for people diagnosed between 2016 and 2022.

By stage, five-year relative survival is 100.0% when the cancer is confined to the breast (64% of cases), 87.5% once it has reached nearby lymph nodes (27%), and 33.8% once it has spread further (6%).

Read those as population averages. They pool every subtype, age, and treatment approach, and they cannot describe an individual. Our breast cancer page explains how those categories are assigned.

Signs that should not wait

Adjuvant chemotherapy only exists because a cancer was found in the first place. Book an appointment for:

• A new lump or firm thickening in the breast or armpit that does not come and go with your cycle.
• Skin dimpling or puckering, or a texture like orange peel.
• A nipple that has newly turned inward, or crusting that will not heal.
• Discharge from one nipple without squeezing, especially if bloody.
• One breast turning red, warm, or swollen over days to weeks.
• Any one-sided change lasting more than two to three weeks.

If you are already in treatment, a temperature at or above 100.4°F (38°C) needs an urgent call, not a next-day appointment. Fever during chemotherapy can mean infection while white cell counts are low.

What this trial cannot tell you

• Median follow-up was only 36 months at this first report. There had been 315 relapses or deaths against 515 expected, and the authors flagged that themselves.
• The abstract reports risk ratios and P-values without confidence intervals for the primary comparison, so the precision of the estimate is hard to judge.
• Every-2-week dosing requires filgrastim injections, which add cost and burden.
• The specific drug program predates HER2-targeted therapy and current taxane scheduling. The dose-dense principle held up; the exact regimen is dated.
• All participants had node-positive disease after surgery. The result does not transfer to node-negative disease or to treatment given before surgery. Trial phases covers what a phase 3 trial is built to answer.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• Citron ML and colleagues, "Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer," Journal of Clinical Oncology, 2003 (PMID 12668651): https://pubmed.ncbi.nlm.nih.gov/12668651/
• SEER Cancer Stat Facts, Female Breast Cancer: https://seer.cancer.gov/statfacts/html/breast.html
• National Cancer Institute, Breast Cancer Treatment (PDQ), health professional version: https://www.cancer.gov/types/breast/hp/breast-treatment-pdq

How this page was made

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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